Article

Stem cell antigen-1 deficiency enhances the chemopreventive effect of peroxisome proliferator-activated receptorγ activation.

Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA..
Cancer Prevention Research (impact factor: 4.91). 09/2011; 5(1):51-60. DOI:10.1158/1940-6207.CAPR-11-0256 pp.51-60
Source: PubMed

ABSTRACT Stem cell antigen-1 (Sca-1, Ly6A) is a glycerophosphatidylinositol (GPI)-anchored protein that was identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem and progenitor cells in various tissues, little is known about its function and associated signaling pathways in normal and malignant cells. Here, we report that the absence of Sca-1 in the mammary gland resulted in higher levels of PPARγ and PTEN, and a reduction of pSer84PPARγ, pERK1/2, and PPARδ. This phenotype correlated with markedly increased sensitivity of Sca-1 null mice to PPARγ agonist GW7845 and insensitivity to PPARδ agonist GW501516. Reduction of Sca-1 expression in mammary tumor cells by RNA interference resulted in a phenotype similar to the Sca-1 deficient mammary gland, as evidenced by increased PPARγ expression and transcriptional activity, resulting in part from a lesser susceptibility to proteasomal degradation. These data implicate Sca-1 as a negative regulator of the tumor suppressor effects of PPARγ.

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    Article: Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell migration.
    Torey D Batts, Heather L Machado, Yiqun Zhang, Chad J Creighton, Yi Li, Jeffrey M Rosen
    [show abstract] [hide abstract]
    ABSTRACT: Stem cell antigen-1 (Sca-1 or Ly6A) is a glycosyl phostidylinositol (GPI)-anchored cell surface protein associated with both stem and progenitor activity, as well as tumor initiating-potential. However, at present the functional role for Sca-1 is poorly defined. To investigate the role of Sca-1 in mammary tumorigenesis, we used a mammary cell line derived from a MMTV-Wnt1 mouse mammary tumor that expresses high levels of endogenous Sca-1. Using shRNA knockdown, we demonstrate that Sca-1 expression controls cell proliferation during early tumor progression in mice. Functional limiting dilution transplantations into recipient mice demonstrate that repression of Sca-1 increases the population of tumor propagating cells. In scratch monolayer assays, Sca-1 enhances cell migration. In addition, knockdown of Sca-1 was shown to affect cell adhesion to a number of different extracellular matrix components. Microarray analysis indicates that repression of Sca-1 leads to changes in expression of genes involved in proliferation, cell migration, immune response and cell organization. Sca-1 exerts marked effects on cellular activity and tumorgenicity both in vitro and in vivo. A better understanding of Sca-1 function may provide insight into the broader role of GPI-anchored cell surface proteins in cancer.
    PLoS ONE 01/2011; 6(11):e27841. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

bone marrow
 
data implicate Sca-1
 
glycerophosphatidylinositol
 
GPI)-anchored protein
 
mammary gland
 
mammary tumor cells
 
negative regulator
 
phenotype correlated
 
PPARγ agonist GW7845
 
PPARγ expression
 
progenitor cells
 
proteasomal degradation
 
PTEN
 
RNA interference
 
Sca-1 deficient mammary gland
 
Sca-1 expression
 
Sca-1 null mice
 
Stem cell antigen-1
 
transcriptional activity
 
tumor suppressor effects